Construction Of MOF-enzyme Nanocatalytic Reaction System For Tumor Microenvironment Lactic Response And Its Antitumor Research

Malignant tumor is one of the few diseases that modern medicine still cannot overcome.A tumor is composed of tumor cells and its microenvironment.Traditional treatment methods(such as chemotherapy,photodynamic therapy,hyperthermia,etc.)as the mainstay in the field of tumor therapy kill tumor cells mainly by the "external force".However,studies on endogenous regulation of tumor microenvironment to enhance anti-tumor effects and inhibit tumor metastasis and recurrence,such as tumor immunotherapy,have also been the focus of many scholars;but the heterogeneity of tumor microenvironment greatly limits related study.With the deepening of such research and the rapid development of nanotechnology,the combined treatment modes of tumor microenvironment regulation have gradually emerged and attracted widespread attention.Therefore,how to use the tumor microenvironment more efficiently and develop a more concise,effective and safe combination of tumor microenvironment regulation therapy will have far-reaching significance.Compared with traditional nanomaterials,metal-organic framework composites have attracted extensive attention due to their large specific surface area,porosity and easy-to-modify structure.A large number of basic researches have been carried out in gas selective adsorption and catalysis.In recent years,it has developed broad application in the field of biomedicine,for example,its large pore size is suitable for encapsulating drugs,and exhibits a high loading efficiency;a relatively unstable coordination bond between a metal and a ligand makes it biodegradable;it can be modified to carry a variety of functional groups using a number of techniques.Therefore,relying on the development of nanotechnology,regulating the levels of lactic acid and reactive oxygen species(ROS)in the tumor microenvironment may become a new tumor treatment strategy,which needs to be discussed in depth.Here,we proposes to construct a LFZ composite nanoparticle loaded with lactate oxidase(LOD)and ferric oxide trioxide(Fe3O4)with mesoporous MOF-ZIF-8 as carrier.The catalytic system and its inhibition to tumors were explored at the level of nuclear animals.Experiment content:1.Firstly,gold(Au NPs)nanoparticles and Fe3O4 nanoparticles are loaded in ZIF-8 nanoparticles by in-situ coprecipitation,and then the gold nanoparticles are removed by selective etching to obtain mesoporous ZIF-8 nanoparticles(FZ NCs)with ferric oxide(Fe3O4)nanoparticles.The loading of lactate oxidase(LOD)can be successfully achieved by using mesopores of FZ NCs.At this time,we have successfully constructed a composite nanocatalytic system(LFZ NCs)that can target lactic acid in tumor microenvironment.LFZ NCs can consume lactic acid and produce hydrogen peroxide.In the weak acid environment of the tumor,the ferric oxide(Fe304)nanoparticles can act as a catalase to catalyze hydrogen peroxide to produce reactive oxygen species.2.In vitro and in vivo evaluated the ability of the composite nanomaterials of killing tumor cells.Firstly,through MTT assay and the apoptosis experiment,we explored the ability of materials to induce tumor cell apoptosis,and then evaluated the ability of materials to induce ROS production,and explored the mechanism of materials killing cells.Finally,the anti-tumor effect of the material was evaluated at the animal level,and the biosafety of the material and the related mechanism of inhibiting tumor growth were explored by tissue staining.